University of Groningen
Urinary sodium evaluation
Damman, Kevin; Ter Maaten, Jozine M; van der Meer, Peter
Published in:
European Journal of Heart Failure
DOI:
10.1002/ejhf.1825
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Damman, K., Ter Maaten, J. M., & van der Meer, P. (2020). Urinary sodium evaluation: the missing target
for diuretic treatment optimization in acute heart failure patients? Reply. European Journal of Heart Failure,
22(10), 1933-1934. https://doi.org/10.1002/ejhf.1825
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
LETTERS TO THE EDITOR
doi:10.1002/ejhf.1 18 4
Online publish-ahead-of-print1April 2020
Urinary sodium evaluation:
the missing target for
diuretic treatment
optimization in acute heart
failure patients? Letter
regarding the article ‘Clinical
importance of urinary
sodium excretion in acute
heart failure’
We read with interest the paper by Damman
et al.1 describing the clinical importance of
early urinary sodium (uNa) excretion in acute heart failure (AHF) patients. We fully agree
with the potential interest of uNa
toring in this context. The strength of uNa
excretion could be its ability to combine, in a single parameter, urinary volume and spot sodium concentration, both target criteria suggested by the Heart Failure Association
therapeutic algorithm of congestive AHF.2
Moreover, it seems to perform even better
as a prognostic predictor than these two indicators considered separately.
However, we have some comments on the paper. The observational design and the
absence of a prospective protocol led to signicant potential biases. For example, an
appraisal of the congestion status at
tation is lacking: an objective evaluation (i.e. “wet score”3) may allow for a more genuine
interpretation of the uNa-independent
nostic role. In fact, admitted patients,
ing on their congestion grade and on doses
and timing of intravenous diuretic
tion in the emergency department, may be
in a different position in the time-natriuresis curve. Another interesting point to be
dated is whether uNa maintains its predictive
role irrespective of baseline ejection fraction
and the use of inotropes/vasopressors, which was not standardized.
Nevertheless, the way through which this parameter would affect mortality
out a solid correlation with heart failure rehospitalizations remains unclear. It would therefore be interesting to evaluate the
association of 6 h uNa excretion with other
surrogated endpoints, such as the incidence of treatment failure, worsening renal function
(WRF) or changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a recent
sub-analysis of the DRAIN randomized
trolled trial, we demonstrated the association between low early uNa spot and worse
diuretic response in patients admitted for acute decompensation of advanced chronic
heart failure with a high risk of diuretic resistance.4,5Early spot uNa 50 mmol/L was
associated with higher levels of NT-proBNP
and a higher incidence of WRF at 72 h,
suggesting worse unloading of these patients
after a standardized therapeutic protocol.
In conclusion, even if we agree on the appealing idea of uNa as a single, low-cost and precocious indicator of AHF outcome,
caution must be taken in the interpretation of
this value, which needs to be contextualized in a global clinical assessment. Prospective
randomized studies are needed to elucidate
if natriuresis only represents a predictor of diuretic response and, eventually, a
tic marker, or may be a therapeutic goal for unloading.
Alessandro Galluzzo1,2,
Maurizio Bertaina2, and Simone Frea2
1Division of Cardiology, Sant’Andrea Hospital, Vercelli, Italy; and2Division of Cardiology,
Città della Salute e della Scienza University
Hospital of Turin, Turin, Italy
* Email: alessandro.galluzzo@unito.it
References
1. Damman K, Ter Maaten JM, Coster JE, Krikken JA, van Deursen VM, Krijnen HK, Hofman M, Nieuwland W, van Veldhuisen DJ, Voors AA, van
der Meer P. Clinical importance of urinary sodium excretion in acute heart failure. Eur J Heart Fail 2020;22:1438– 447.1
2. Mullens W, Damman K, Harjola VP, Mebazaa A,
Brunner-La Rocca HP, Martens P, Testani JM, Tang
WH, Orso F, Rossignol P, Metra M, Filippatos G,
Seferovic PM, Ruschitzka F, Coats AJ. The use of
diuretics in heart failure with congestion – a posi-tion statement from the Heart Failure Associaposi-tion
of the European Society of Cardiology. Eur J Heart Fail 20 9;1 21:137–155.
3. Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JE, Cleland JG, Dickstein K, Drazner
MH, Fonarow GC, Jaarsma T, Jondeau G, Sendon JL, Mebazaa A, Metra M, Nieminen M, Pang PS,
Seferovic P, Stevenson LW, van Veldhuisen DJ,
Zannad F, Anker SD, Rhodes A, McMurray JJ,
patos G. Assessing and grading congestion in acute
heart failure: a scientic statement from the Acute
Heart Failure Committee of the Heart Failure
Association of the European Society of Cardiology
and endorsed by the European Society of Intensive
Care Medicine. Eur J Heart Fail 2010;12:423–433.
4. Frea S, Pidello S, Volpe A, Canavosio FG, Galluzzo A,
Bovolo V, Camarda A, Golzio PG, D’Ascenzo F,
Bergerone S, Rinaldi M, Gaita F. Diuretic treatment in high-risk acute decompensation of advanced
chronic heart failure – bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial. Clin Res Cardiol 2020;109:417–425.
5. Galluzzo A, Frea S, Boretto P, Pidello S, Volpe A,
Canavosio FG, Golzio PG, Bergerone S, De Ferrari
GM. Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hypona-tremia: insights from DRAIN trial. Clin Res Cardiol 2020;109:1 1 125 – 259.
doi:10.1002/ejhf.1825
Online publish-ahead-of-print 16 April 2020
Urinary sodium evaluation:
the missing target for
diuretic treatment
optimization in acute heart
failure patients? Reply
Dr Galluzzo et al. commented on our
script on urinary sodium content after diuretic initiation in acute heart failure (HF).1 They
expressed their concerns on the absence
of a prospective protocol and the fact that
there was no estimate of congestion (score) available. The Authors suggest that given these limitations, patients could have been
presenting at different positions at the
natriuresis’ curve. Certainly, we acknowledge that the observational nature of our study
is a limitation.1 However, our ndings are
a reection of ‘real-world’ data, which also inherently means that there was no structural
scoring of congestion at start of treatment. It
is also important to realize that our primary
ndings were based on 6 h urinary sodium content. Although many patients improve
clinically during the rst hours of treatment, it is not likely assessment of congestion at baseline would have altered our ndings at
6 h. We did show that patients who had lower urinary sodium content at 6 h had
evidence of more severe HF with higher
natriuretic peptide levels at baseline, lower blood pressure, worse renal function, more
frequent use of loop diuretics at baseline and
more use of inotropes and vasopressors.
© 2020 European Society of Cardiology
Printed by [Bibliotheek Rijksuniversiteit - 129.125.166.037 - /doi/epdf/10.1002/ejhf.1825] at [08/1
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
1934
Letters to the Editor
The Authors point to their subanalysis of
the small DRAIN study in 80 patients, where
they evaluated early (2 h) spot urinary sodium content and surrogate outcome measures and
found similar results as compared with our analyses.2Our results should be interpreted
slightly different, considering we evaluated total urinary sodium content over 6 h, which
is probably a better representation of total
natriuretic response to a given diuretic dose than spot urinary sodium.3–5 With regard
to the inotrope/vasopressor regimen not being standardized in our cohort, we con-sider these therapies only in very selected
patients, according to the European Society of Cardiology HF guidelines, where they are
only advocated in a small proportion of acute HF patients with severe hypotension.6In our
study, the prognostic information of urinary
sodium content at 6 h was unchanged by adjusting for inotrope/vasopressor use [haz-ard ratio (HR) 1.05, 95% condence interval
(CI) 1 1 1.0 – .08, P =0.008, per 10 mmol
decrease (n = 146)] or left ventricular
tion fraction [(HR 1.05, 95% CI 1 1 1.0 – .08,
P= 0.003, per 10 mmol decrease (n= 157)].
Change in natriuretic peptide level was only
available in a subset of patients at 24 h after admission, and was not different in tertiles
of urinary sodium (P = 0.69 and P = 0.67 for absolute and relative change, respectively).
We do not think worsening renal func-tion (WRF), as used by the Authors, is an appropriate surrogate endpoint in acute HF patients without considering natri-uretic/diuretic response. WRF in a patient
with good natriuresis is not true WRF and
should be termed pseudo-WRF, and cannot
directly be compared with WRF in patients with poor natriuresis/diuretic response,
according to most recent position papers on how to evaluate renal function in HF.7,8
For instance, in our cohort and using dif-ferent denitions, WRF was consistently more frequent in patients with the highest
urinary sodium content at 6 h. Yet, the
prognostic information of urinary sodium
at 6 h was unaffected by the occurrence of WRF, and WRF itself was not independently associated with clinical outcome. This again
highlights not to use serum creatinine/WRF
as a response marker during decongestion in acute HF.
Finally, the nding that urinary sodium
tent at 6 h was only associated with all-cause
mortality and appeared not to be associated
with HF readmission is probably related to
the severity of HF in our tertiary HF clinic, as
well as a tendency of some elderly patients
with HF at our clinic to decide not to be read-mitted after discharge as part of advanced care planning. Therefore, we also evaluated
the combined endpoint of mortality and HF rehospitalization, conrming our primary results. We agree with the Authors that we need prospective randomized studies to evaluate whether this cheap and easy marker
of natriuretic/diuretic response is a valuable
tool to assess treatment effect or can serve
as therapeutic target in a cute HF.
Kevin Damman,
Jozine M. Ter Maaten, and Peter van der Meer
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
*Email: k.damman@umcg.nl
References
1. Damman K, Ter Maaten JM, Coster JE, Krikken JA, van Deursen VM, Krijnen HK, Hofman M, Nieuwland W, van Veldhuisen DJ, Voors AA, van
der Meer P. Clinical importance of urinary sodium excretion in acute heart failure. Eur J Heart Fail 2020;22:1438– 447.1
2. Galluzzo A, Frea S, Boretto P, Pidello S, Volpe A,
Canavosio FG, Golzio PG, Bergerone S, De Ferrari
GM. Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hypona-tremia: insights from DRAIN trial. Clin Res Cardiol 2020;109:1 1 125 – 259.
3. Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, Tang WH. Insufcient natriuretic response to continuous intravenous
furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail 20 4;1 20:392–399.
4. Honda S, Nagai T, Nishimura K, Nakai M, Honda Y,
Nakano H, Iwakami N, Sugano Y, Asaumi Y, Aiba T,
Noguchi T, Kusano K, Yokoyama H, Ogawa H,
Yasuda S, Anzai T; NaDEF Investigators. Long-term prognostic signicance of urinary sodium
centration in patients with acute heart failure. Int J Cardiol 20 8;1 254:189– 94.1
5. Biegus J, Zymlinski R, Sokolski M, Todd J, Cotter G,
Metra M, Jankowska EA, Banasiak W, Ponikowski P.
Serial assessment of spot urine sodium predicts effectiveness of decongestion and outcome in
patients with acute heart failure. Eur J Heart Fail 20 9;1 21:624–633.
6. Ponikowski P, Voors AA, Anker SD, Bueno H,
Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C,
Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH,
van der Meer P. 2016 ESC Guidelines for the
sis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment
of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure
ation (HFA) of the ESC. Eur J Heart Fail 2016;18: 89 –975.1
7. Mullens W, Damman K, Testani JM, Martens P, Mueller C, Lassus J, Tang WHW, Skouri H, Ver-brugge FH, Orso F, Hill L, Dilek U, Lainscak M,
Rossignol P, Metra M, Mebazaa A, Seferovic P,
Ruschitzka F, Coats A. Evaluation of kidney function
throughout the heart failure trajectory – a position statement from the Heart Failure Association of
the European Society of Cardiology. Eur J Heart Fail 2020;22:584–603.
8. Mullens W, Damman K, Harjola VP, Mebazaa A,
Brunner-La Rocca HP, Martens P, Testani JM, Tang
WH, Orso F, Rossignol P, Metra M, Filippatos G,
Seferovic PM, Ruschitzka F, Coats AJ. The use
of diuretics in heart failure with congestion – a position statement from the Heart Failure
ation of the European Society of Cardiology. Eur J Heart Fail 20 9;1 21:137– 55.1
doi:10.1002/ejhf.1852
Online publish-ahead-of-print 30 April 2020
Effects of vericiguat in heart
failure with reduced ejection
fraction: do not forget sST2.
Letter regarding the article
‘Baseline features of the
VICTORIA (Vericiguat
Global Study in Subjects with
Heart Failure with Reduced
Ejection Fraction) trial’
We read with interest the paper by Pieske
et al.1describing the baseline characteristics
of patients enrolled in the VICTORIA (Veri-ciguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. Despite the quite extensive description of patient characteristics at baseline, no infor-mation about heart failure (HF) biomarkers other than natriuretic peptides is available. Specically, data about high-sensitivity cardiac troponin T (hs-cTnT) and soluble suppres-sion of tumorigenesis-2 (sST2) have not been provided, although these biomarkers yield strong and independent prognostic signicance beyond natriuretic peptides for
the prediction of all-cause and cardiovascular mortality and HF hospitalization in patients with chronic HF, particularly those with HF and reduced ejection fraction (HFrEF).
While hs-cTnT will be analysed in a planned
post-hoc analysis of the VICTORIA trial, sST2
apparently will not.2 This attitude of study
investigators may be related to the results of the SOCRATES-PRESERVED (Soluble
Guanylate Cyclase Stimulator in Heart Failure Patients with Preserved Ejection Fraction)
trial, where no change in sST2 levels was
observed, although this was in line with the
overall trend of other cardiac biomarkers in this study population, including natriuretic peptides.3 Conversely, sST2 was not
ated in the SOCRATES-REDUCED (Soluble
© 2020 European Society of Cardiology
Printed by [Bibliotheek Rijksuniversiteit - 129.125.166.037 - /doi/epdf/10.1002/ejhf.1825] at [08/1
